Method for provoking angiogenesis by administration of angiogenically active oligosaccharides

Abstract

A method for causing or increasing angiogenesis is described. The method involves administering to a subject, such as a human being in need of angiogenesis an angiogenically effective amount of an angiogenically effective, pharmaceutically acceptable oligosaccharide or mixture of oligosaccharides.

We claim: 
     
       1. Method for causing or enhancing angiogenesis in a subject in need thereof, comprising administering to said subject an angiogenically effective amount of at least one angiogenically active oligosaccharide. 
     
     
       2. Method of claim 1, wherein said oligosaccharide is a tetrasaccharide. 
     
     
       3. Method of claim 2, wherein said tetrasaccharide is selected from the group consisting of O-α-D-glucopyranosyl-(1→6)-O-α-D-glucopyranosyl-(1.fwdarw.4-O-α-D-glucopyranosyl-(43 4) 1→4)-D-glucose, O-(2-Acetamido-2-deoxy-β-D-glucopyranosyl-(1→4)-O-2 (2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)2-acetamido-2-deoxy-D-glucose (N,N',N",N'"-Tetraacetyl chitotetraose),   and 2-(2-Carbomethoxyethylthio)ethyl-O-α-D-glucopyranosyl-(1→6)-O-α-D-glucopyranosyl-(1→4)-O-α-D-glucopyranosyl-(1.fwdarw.4)-β-D-glucopyranoside.   
     
     
       4. Method of claim 1, wherein said oligosaccharide is a trisaccharide. 
     
     
       5. Method of claim 4, wherein said trisaccharide is selected from the group consisting O-(2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→4)-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)-2-acetamido-2-deoxy-D-glucose (N,N',N"-Triacetyl chitotriose),   O-β-D-Galactopyranosyl-(1→4)-O-β-D-galactopyranosyl-(1.fwdarw.4)-D-glucose,   Ethyl O-α-D-galactopyranosyl-(1→4)-O-β-D-galactopyranosyl-(1.fwdarw.4)β-D-glucopyranoside,   Ethyl O-α-D-galactopyranosyl-(1→4)-O-β-D-galactopyranosyl-(1.fwdarw.4)-2-acetamido-2-deoxy-β-D-glucopyranoside,   and Methyl O-α-D-mannopyranosyl-(1→6)-[O-α-D-mannopyranosyl-(1.fwdarw.3)-α-D-mannopyranoside.   
     
     
       6. Method of claim 1, wherein said oligosaccharide is a disaccharide. 
     
     
       7. Method of claim 6, wherein said disaccharide is selected from the group consisting of Methyl O-β-D-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside,   Ethyl O-α-D-galactopyranosyl-(1→4)-O-β-D-galactopyranoside,   2-(Octadecylthio)ethyl O-α-D-galactopyranosyl-(1→4)-β-D-galactopyranoside,   Methyl O-(2-acetamide-2-deoxy-β-D-galactopyranosyl)-(1→3)-α-D-galactopyranoside,   O-(2-Acetamido-2-deoxy-β-D-glucopyranosyl)-(1→4)-2-acetamido-2-deoxy-D-glucose (N,N'-Diacetyl chitobiose),   Methyl O-α-D-galactopyranosyl-(1→3)-α-D-galactopyranoside,   and Methyl O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside.   
     
     
       8. Method of claim 1, comprising administering a mixture of oligosaccharides to said subject. 
     
     
       9. Method of claim 8, wherein said mixture of oligosaccharides is derived from human milk. 
     
     
       10. Method of claim 9, wherein said mixture of oligosaccharides contain lactose. 
     
     
       11. Method of claim 9, wherein said mixture of oligosaccharides contains lacto-N-neotetraose. 
     
     
       12. Method of claim 9, wherein said mixture of oligosaccharides contains lactodifucotetraose. 
     
     
       13. Method of claim 9 wherein said mixture of oligosaccharides contains lacto-N-fuco pentaose II. 
     
     
       14. Method of claim 1, wherein said subject is a human being. 
     
     
       15. Method of claim 1, wherein said oligosaccharide is administered in an amount ranging from about 100 μg to about 20 mg per day. 
     
     
       16. Method of claim 1, wherein said oligosaccharide contains only glucose residues. 
     
     
       17. Method of claim 1, wherein said oligosaccharide contains only galactose residues. 
     
     
       18. Method of claim 1, wherein said oligosaccharide contains only mannose residues. 
     
     
       19. Method of claim 1, wherein said oligosaccharide contains a mixture of at least two of glucose, galactose, and mannose residues. 
     
     
       20. Method of claim 1, wherein said oligosaccharide is conjugated to bovine serum albumin. 
     
     
       21. Method of claim 20, wherein said oligosaccharide complexed to obvine serum albumin is selected from the group consisting of O-β-(2-(2-carbomethoxyethylthio)ethyl)-N-acetyl-D-galactosamine; O-β-(2-(2-carboxymethoxyethylthio)ethyl-N-acetyl-D-glucosamine; O-2-(2-carbomethoxylethylthio)ethyl-methyl; and O-β-(2-(2-carboxymethoxyethylthio)ethyl galactose 1→3 N-acetyl glucosamine. 
     
     
       22. Method of claim 1, wherein said oligosaccharide is a substituted monosaccharide selected from the group consisting of 2-(2-Carbomethoxyethylthio)ethyl-β-D-galactopyranoside,   2-l -(Octadecylthio)ethyl-β-D-galactopyranoside,   2-(2-Carbomethoxyethylthio)ethyl-β-D-glucopyranoside,   and 2-(Octadecylthio)ethyl-β-D-glucopyranoside.